Head and neck squamous cell carcinoma (HNSCC) is among the ten most frequent types of cancer. Mortality is high, especially in cases that are resistant to the usual treatment with cisplatin-based chemotherapy. A study led by the Biomedical Research in Cancer Stem Cells group at Vall d'Hebron Research Institute (VHIR) has studied the molecular mechanisms related to resistance to treatment with the aim of identifying new therapeutic targets. The study, published in the journal Cancers, has been carried out in collaboration with the University of Barcelona, Eurecat – Centre for Omic Sciences (COS) – Rovira i Virgili University, Instituto de Investigación Sanitaria de Santiago de Compostela, Fundación de Medicina Genómica from Santiago de Compostela, Virginia Commonwealth University (USA), CIBER of Oncology (CIBERONC) and CIBERER of Rare Diseases (CIBERER).

The researchers conducted a RNA sequencing and proteomics study to compare cells sensitive and resistant to cisplatin treatment. "These are relevant strategies to understand the mechanisms involved in resistance and to find new biomarkers and therapies to prevent the acquisition of resistance to treatment", says Dr. Matilde E. LLeonart, head of the Biomedical Research in Cancer Stem Cells group at VHIR.

The work was performed on pharyngeal tumor cell lines, metastatic pharyngeal cells and laryngeal tumor cells. In this way, more than 100 genes with different expression depending on whether the cells were resistant or sensitive to treatment were identified. Of all the genes identified, 12 were chosen according to their known role in the development of HNSCC. These were analyzed in samples from patients at Vall d'Hebron Hospital with laryngeal cancer.

Among the results in patient samples, the finding of elevated MAGEB2 expression in cisplatin-resistant tumors is noteworthy, showing its involvement in the acquisition of resistance. In addition, inhibition was found to make the cells sensitive to treatment again. "Our study shows that MAGEB2 could be a potential therapeutic target in cancer therapy to favor response to standard chemotherapy", concludes Dr. LLeonart.
The work has been funded by the Instituto de Salud Carlos III (ISCIII) with European Regional Development Funds (ERDF) and the Spanish Association Against Cancer (AECC).